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Apoptosis. 2007 Aug;12(8):1503-10.

Smac/DIABLO is required for effector caspase activation during apoptosis in human cells.

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Department of Molecular Biology, Max Planck Institute for Infection Biology, Charit├ęplatz 1, 10117, Berlin, Germany.


Mitochondria play a pivotal role during stress-induced apoptosis as several proapoptotic proteins are released to the cytosol to activate caspases. Smac/DIABLO is one of the proapoptotic proteins released from the mitochondria and has been shown to inactivate IAPs. However, gene knockout studies in mice revealed a redundant role for Smac during development and cell death. By applying RNA interference-mediated loss of function approach, we demonstrate that Smac/DIABLO is required for the activation of effector but not initiator caspases during stress and receptor-mediated cell death in HeLa cells. Cells with reduced Smac resist apoptosis and retained clonogenicity. Our results suggest an obligatory role for Smac/DIABLO in these tumor cells during several pathways of apoptosis induction.

[Indexed for MEDLINE]

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